Related Experiment Video
Updated: Jun 28, 2026
06:23
Detection of Nuclear Blebbing and DNA Leakage in Mammalian Cells by Immunofluorescence
Published on: January 17, 2025
[A-type lamins and progeroïd syndromes : persistent farnesylation with dramatic effects]
Claire L Navarro1, Yannick Poitelon, Nicolas Lévy
1Université de la Méditerranée, Inserm UMR 910, Génétique Médicale et Génomique Fonctionnelle, Faculté de médecine de Marseille 27, boulevard Jean Moulin, 13005 Marseille, France.
Medecine Sciences : M/S
|October 28, 2008
Summary
Hutchinson-Gilford Progeria (HGPS) and Restrictive Dermopathy (RD) are laminopathies caused by defects in Lamin A maturation. These disorders lead to toxic intranuclear accumulation of Lamin A precursors, impacting nuclear homeostasis.
Area of Science:
- Cell Biology
- Genetics
- Molecular Biology
Context:
- Hutchinson-Gilford Progeria (HGPS) and Restrictive Dermopathy (RD) are rare genetic disorders.
- These conditions are classified as Laminopathies, affecting the Lamin A maturation pathway.
- Altered Lamin maturation leads to premature aging features and neonatal lethality.
Purpose:
- To review the structure and function of A-type Lamins.
- To explore the pathophysiology of HGPS, RD, and MAD disorders.
- To discuss current animal models and potential therapeutic strategies for Laminopathies.
Summary:
- HGPS and RD result from aberrant splicing or enzyme inactivation (ZMPSTE24/FACE1) in Lamin A processing.
- Both conditions involve the toxic accumulation of unprocessed Lamin A precursors within the nucleus.
- This accumulation disrupts nuclear homeostasis, leading to disease phenotypes.
Impact:
- Understanding Lamin A processing is crucial for comprehending these severe genetic disorders.
- This review highlights shared pathophysiological mechanisms in distinct Laminopathies.
- Insights may guide the development of novel therapeutic approaches targeting nuclear homeostasis.
Related Concept Videos
03:03Amyloid Fibrils
Amyloid fibrils are aggregates of misfolded proteins. Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils.
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
03:03Amyloid Fibrils
Amyloid fibrils are aggregates of misfolded proteins. Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils.
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
01:31Types of Intermediate Filaments
The intermediate filaments are an essential component of the cytoskeleton. Presently six types of intermediate filament have been identified. Type I and II are acidic and basic keratin proteins. Type III is of mesodermal origin and comprises four proteins: vimentin, desmin, glial fibrillary acidic protein (GFAP), and peripherin. Vimentin is commonly found in mesenchymal cells, desmin in muscle cells, GFAP in astrocytes, while peripherin is found in peripheral nervous system neurons (PNS). Type...
01:09Cytoskeletal Linker Proteins - Plakins
Plakins are large proteins with binding domains for microtubules, microfilaments, intermediate filaments, and membrane-associated protein complexes at cell junctions. Plakin functions are evolutionarily conserved and are primarily involved in organizing the different components of the cytoskeleton by crosslinking them to each other and connecting them to the cell-matrix and cell adhesion complexes. They are also known to interact with signal transducers, serve as scaffolds for signaling...
01:19Actin Filament Depolymerization
Actin filaments (F-actin) are composed of actin subunits. The dissociation of actin monomers can occur from either end of F-actin. The rate of dissociation is faster from the minus-end or the pointed end, where the actin subunits exist with a bound ADP, together known as ADP-actin. The depolymerization of F-actin is aided by proteins, including the actin-depolymerizing factor (ADF) and cofilin family of proteins, gelsolin, and glia maturation factor (GMF).
In F-actin, the ADF/cofilin proteins...
In F-actin, the ADF/cofilin proteins...
01:22Lysosomal Hydrolases
Lysosomes are the site for the degradation of macromolecules and biological polymers released during membrane trafficking events such as secretory, endocytic, autophagic, and phagocytic pathways. The membrane-enclosed area of the lysosome, called the lumen, contains hydrolytic enzymes active in an acidic environment. These acid hydrolases are functional at a pH between 4.5 and 5 and are involved in cellular processes such as cell signaling, energy metabolism, restoration of the plasma membrane,...